Robinson D R, Wu Y M, Kalyana-Sundaram S, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by  integrative sequencing. Nat Genet. 2013,45(2): 180-185.

A 44-year old woman with recurrent solitary fibrous tumor (SFT)/hemangiopericytoma was enrolled in a clinical sequencing program including whole-exome and transcriptome sequencing. A gene fusion of the transcriptional repressor NAB2 with the transcriptional activator STAT6 was detected. Transcriptome sequencing of 27 additional SFTs identified the presence of a NAB2-STAT6 gene fusion in all tumors. Using RT-PCR and sequencing, we detected this fusion in all 51 SFTs, indicating high levels of recurrence. Expression of NAB2-STAT6 fusion proteins was confirmed in SFT, and the predicted fusion products harbor the early growth response (EGR)-binding domain of NAB2 fused to the activation domain of STAT6. Overexpression of the NAB2-STAT6 gene fusion induced proliferation in cultured cells and activated the expression of EGR-responsive genes. These studies establish NAB2-STAT6 as the defining driver mutation of SFT and provide an example of how neoplasia can be initiated by converting a transcriptional repressor of mitogenic pathways into a transcriptional activator.
作者对一位44岁复发性孤立性纤维性肿瘤（SFT）/血管外皮细胞瘤的女性患者，进行了包括全部外显子组和转录组在内的基因测序，检测到了转录抑制因子NAB2和转录激活因子STAT6的融合。另外在对其它27个SFTs的转录组测序中，所有肿瘤中均出现了NAB2-STAT6基因融合的现象。通过RT-PCR和测序技术，作者在全部检测的51个SFTs中均检测到了NAB2-STAT6基因的融合，提示NAB2-STAT6基因融合在SFTs中有较高的发生频率。同时证实了SFT中存在NAB2-STAT6融合蛋白的表达，提示早期生长应答（EGR）结合域NAB2融合到STAT6活化的结构域从而产生了相应的融合产物。NAB2-STAT6基因融合的过度表达能够诱导体外培养细胞的增殖，并且激活EGR相关应答基因的表达。这些研究表明NAB2-STAT6在启动突变SFT的发生过程中起着决定性的作用，阐明了肿瘤在有丝分裂过程中通过改变转录抑制因子成为转录激活因子，最终为肿瘤的如何形成提供了一个非常有用的案例。